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Cell access
Written by Tim Sheppard MBBS BSc. Created 10/1/10; last updated 14/8/12

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How do things get into cells?

In order for cells to work properly, things need to get in and out of them. Chemicals are produced that need to be taken elsewhere (e.g. hormones), and other chemicals are needed to be brought in to be used in a particular reaction. There are lots of ways that something can gain access to a cell, some of which happen nice and easily, and others which require lots of energy to achieve.

The simplest is passive diffusion. This works for very small chemicals with very little charge or polarity. These can just float through the cell membrane without getting stopped. An example of this is water (in osmosis); water molecules can float between the fatty acids and pass in or out of the cell, depending on the concentration in and out of the cell.

Sometimes things don't fit so easily. If they have a charge, or they're a bit too big, they may need special proteins in the middle of the membrane to help them through. Examples of these include ion channels or transporters. Other times they're simply too big to squeeze through, and so they get in and out in envelopes of membrane - known as endocytosis or exocytosis.

The more complicated a process is, the more likely it is to need energy. Simple diffusion just follows a concentration gradient (from high concentration to low concentration). On the other hand, secondary active transport uses ATP to move sodium and potassium in order to move chemicals in the opposite direction to their natural flow.

What are ion channels?

Ion channels are routes through the membrane that allow ions to pass through. Put most simply, they're essentially just a thin corridor of water that links the inside of the cell with the outside of the cell, just big enough to allow a tiny ion to pass through. However, they need a clever design to allow ions to pass through a membrane which would otherwise prevent any charged particles to pass, and they come in different types.

Some ion channels will be charge-specific - they'll let almost anything through, so long as it has the right kind of charge (i.e. positive of negative). Others will be ion-specific - they'll only let a specific kind of ion through, such as a sodium ion (Na+) or a calcium ion (Ca2+).

Some will be constantly open, always allowing the passage of ions through the pore in the middle. Others will be gated - for example, voltage-gated ion channels, which are involved in forming an action potential, and only open when the voltage across the membrane changes. Gates can also be controlled by temperature, or by mechanical force (e.g. in baroreceptors).

The movement of ions is crucial to almost everything that happens in the body. Ion channels are particularly important in controlling the voltage across a membrane. The concentration of ions on each side of a membrane is what determines the resting membrane potential, and changes in these concentration leads to depolarisation - as in an action potential. Since some ion channels only open in response to certain chemicals, they are able to form receptors known as ionotropic receptors - stimulating an electrical response. In short, activity within cells depends on ion channels.

What are transporters?

Transporters are proteins which sit in the membrane and help substances to pass into the cell. They're usually specific - they're only there to help one chemical to pass through - but they still come in different types. Some are there for facilitated diffusion; others are there for active transport.

The protein obviously needs to go across a membrane completely in order to transport the substance completely in or out of the cell. They consequently sit somewhere in the membrane, and have a specific active site like in an enzyme, which receives the chemical before transporting it to the other side.

What is facilitated diffusion?

If a chemical is too big or polarised to fit through the membrane normally, it can still get in without using up any energy. All it needs is a transporter which will allow it to shift into the cell, down its concentration gradient.

For example, if there is lots of a susbtance outside a cell but not very much inside, the transporter can provide a kind of channel into the cell. It receives the substance and carries it through, in the same direction that diffusion would allow it to travel.

This is called facilitated diffusion because the substance couldn't travel without help. It's too big to pass through a partially permeable membrane, but it still wants to get across. The transporter helps - or facilitates - the diffusion process.

What is active transport?

Sometimes a chemical needs to travel in the opposite direction to the concentration gradient. Neither passive diffusion nor facilitated diffusion will work, because the chemical already has a high concentration in its destination. Take, for example, the cell is trying to pump sodium out of a cell. There's already loads of sodium outside the cell - and not very much inside. In order to keep pumping sodium against the concentration gradient, the transporter needs to use up energy. This isn't a passive process - instead, it's an active process, hence the name: active transport.

A very common example of this is the sodium-potassium pump (or sodium-potassium ATPase). Every time an action potential works its way across a membrane, sodium has leaked into a cell and potassium has leaked out. You need to maintain the difference in concentrations inside and outside the cell in order to make sure that the next action potential can form, so you have to pump ions back - even though you're pumping in the opposite direction to diffusion. Energy, in the form of ATP, is used to actively pump the ions in the opposite direction to their concentration gradients.

What is a co-transporter?

Some transporters are set-up to carry two chemicals at once. In this case, it's called a co-transporter. Both chemicals are received on one side of the membrane and transported through to the other.

Co-transporters are particularly clever because they use one substance that's going with its concentration gradient to transport another one that's going against it's concentration gradient. It's a bit like the first substance enthusiastically grabs hold of its friend and pulls it along with it. While the first substance is going in the right direction, the second one gets dragged along with it - enabling transport in the opposite direction to diffusion.

The classic example of this is the sodium-glucose co-transporter in the gut. Glucose has got a fairly low concentration in the gut compared to the inside of a cell, but you still need to absorb it; the body cleverly does this by transporting it alongside sodium. Sodium has got a high concentration outside the cell and a low concentration inside; so sodium and glucose are transferred together - one using its concentration gradient (sodium), the other travelling against it.

Co-transporters are also very important in the kidney.

What is secondary active transport?

Secondary active transport is where active transport is used to set up a concentration gradient for a co-transporter to work.

A co-transporter uses the concentration gradient of one chemical (substance A) to transport something else (substance B) against it's concentration gradient. However, substance A needs to maintain its concentration gradient in order for the co-transport to work. So active transport is used to maintain the concentration gradient of the first chemical, so both can be transported back across.

This might sound unnecessarily complicated, but sometimes it's easier to actively transport substance A than it is to actively transport substance B. For example, it might be easier to set up a favourable sodium concentration gradient and to co-transport it with glucose than to simply actively transport glucose.

Indeed, in the body, secondary active transport will often involve something like the sodium-potassium pump. The sodium-potassium pump uses up energy to transport sodium out of the cell and potassium into the cell, but in doing so, it creates a sodium concentration gradient which can be used to transport other chemicals back in using a co-transporter. This is especially true in the kidney.

What is endocytosis?

When you're trying to get particularly big molecules or groups of molecules into a cell, you can use a process called endocytosis. This is where the molecules approach the outside of the cell and are enveloped by the membrane to form a membrane bubble that floats into the cell - a vesicle.

Usually having been recognised by some kind of protein receptor on the surface of the cell, endocytosis occurs to allow the large molecule or group of molecules access into the cell.

There are specific types of endocytosis which give a little more detail. These include the following:

Pinocytosis doesn't require a receptor, because it tends to involve the absorption of fluid (and any solutes in it) from outside the cell. It is a 'blind' way of bringing contents in from the outside. It forms small vesicles which may join with other vesicles specially designed to break up anything nfound in the fluid.

Phagocytosis involves specific molecules being absorbed into cells, recognised by a receptor on the outside so that the right thing is brought in. The vesicle which is formed contains enzymes to break down - or phagocytose - the contents.

What is exocytosis?

Exocytosis is where a vesicle containing a substance destined for the outside of the cell approaches the edge of the cell, and the vesicle's membrane fuses with the cell membrane, forcing the contents out into the outside world. In other words, exocytosis is basically the opposite of endocytosis.

As well as getting into a cell, some substances need to get out of a cell. In order to do this, they can use the channels and transporters already mentioned, but if they're too big or you want to get rid of a whole load of them, you can send them out using exocytosis.

As well as ejecting contents out into the open, exocytosis can also be used to get proteins into the cell membrane. A protein is produced much as normal at the rough endoplasmic reticulum, embedded in the membrane of a vesicle which travels to the edge of the cell. As the vesicle membrane fuses with the cell membrane, the protein embedded in the vesicle membrane becomes a part of the cell membrane. Clever, huh?

Exocytosis is a crucially important process which happens a lot - for example, to signal an action potential at a nerve synapse.

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